Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome

Cell Metab. 2019 Oct 1;30(4):800-823.e7. doi: 10.1016/j.cmet.2019.08.020. Epub 2019 Sep 12.

Abstract

Although antibiotics disturb the structure of the gut microbiota, factors that modulate these perturbations are poorly understood. Bacterial metabolism is an important regulator of susceptibility in vitro and likely plays a large role within the host. We applied a metagenomic and metatranscriptomic approach to link antibiotic-induced taxonomic and transcriptional responses within the murine microbiome. We found that antibiotics significantly alter the expression of key metabolic pathways at the whole-community and single-species levels. Notably, Bacteroides thetaiotaomicron, which blooms in response to amoxicillin, upregulated polysaccharide utilization. In vitro, we found that the sensitivity of this bacterium to amoxicillin was elevated by glucose and reduced by polysaccharides. Accordingly, we observed that dietary composition affected the abundance and expansion of B. thetaiotaomicron, as well as the extent of microbiome disruption with amoxicillin. Our work indicates that the metabolic environment of the microbiome plays a role in the response of this community to antibiotics.

Keywords: antibiotics; diet; dysbiosis; metabolism; metagenomics; metatranscriptomics; microbiome; tolerance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amoxicillin / pharmacology*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacteroides thetaiotaomicron / drug effects*
  • Bacteroides thetaiotaomicron / metabolism*
  • Dietary Fiber / metabolism
  • Drug Resistance, Bacterial*
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Glucose / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Polysaccharides / metabolism

Substances

  • Anti-Bacterial Agents
  • Dietary Fiber
  • Polysaccharides
  • Amoxicillin
  • Glucose